pyridine-3-sulfonyl chloride

Chemical Properties

It is a colorless, transparent liquid. It is extremely unstable when in contact with water and is easily hydrolyzed to generate pyridine-3-sulfonic acid and hydrochloric acid, which makes it lose its reactivity.

Uses

3-pyridinesulfonyl Chloride is a reagent used in the synthesis of pyrimidine derivatives with anti-proliferative activity against negative breast cancer cells.

Application

Pyridine-3-sulfonyl chloride is an essential medical intermediate and is widely applied to the synthesis of medicines, wherein the pyridine-3-sulfonyl chloride is mainly used for preparing TAK-438 (vonoprazan fumarate), which is a novel orally active potassium-competitive acid blocker, developed as an antisecretory drug.

Toxicology

Pyridine-3-sulfonyl chloride causes burns of eyes, skin and mucous membranes. Contact with water liberates toxic gas.

Synthesis

Add thionyl chloride to the water, cool to about 0-5°C, and add cuprous chloride. Fluoboric acid diazonium salt was added to the solution and reacted at 0-5°C overnight. The reaction solution was extracted with dichloromethane, combining the organic layers. The organic layer was washed once with saturated aqueous sodium bicarbonate solution, once with water, and finally once with saturated brine. The product was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated to remove methylene chloride to obtain the product pyridine-3-sulfonyl chloride with a yield of 90.7%.

References

[1] Journal of the American Chemical Society, 1992, vol. 114, # 12, p. 4889 - 4898
[2] Patent: US2006/217387, 2006, A1. Location in patent: Page/Page column 25
[3] Journal of Medicinal Chemistry, 1999, vol. 42, # 13, p. 2409 - 2421
[4] Patent: CN106432067, 2017, A. Location in patent: Paragraph 0090
[5] Patent: WO2016/90317, 2016, A1. Location in patent: Page/Page column 73